摘要:

AbstractMurine susceptibility to ethyl carbamate‐induced carcinogenesis is strain dependent. In vivo sister chromatid exchange (SCE) responses to ethyl carbamate were evaluated in bone marrow cells of gravid adenoma‐susceptible (ICR/Jcl), and resistant (C57Bl/6J) and (DBA/2J) murine dams, as well as in liver cells of their respective ICR/Jcl, C57Bl/6J × DBA/2J (BDF1), and DBA/2J × C57Bl/6J (BDF), fetuses following a single intravenous injection of 1.1, 2.2, or 3.3 mmol/kg of ethyl carbamate on gestation day 13/14. Bone marrow tissues of C57Bl/6J and DBA/2J, but not ICR/Jcl dams, demonstrated greater sensitivity to SCE induction than liver cells of their respective fetuses. Furthermore, relative SCE responses in bone marrow among dams indicated greater sensitivity of the more tumor‐susceptible ICR/Jcl and C57Bl/6J strains to SCE induction by ethyl carbamate relative to the more tumor‐resistant DBA/2J strain. In addition, concurrent alterations (stimulation or inhibition) of bone marrow cell cycle kinetics by ethyl carbamate were consistent with hormone‐related, strain‐dependent hematopoietic stress dur

ISSN:0270-3211    

DOI:10.1002/tcm.1770100102

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1990

数据来源: WILEY

摘要:

AbstractThe effect of ambient temperature and running activity on fetal outcome was studied in CD‐1 mice. Pregnant mice were allowed to be active in a running wheel at various ambient temperatures (26, 30, 32, 34, or 36°C) for 100 min a day. The dams were killed near term, and various maternal and fetal measures made. Mean deep body temperature (measured using radio‐telethermometers implanted in the abdomen) of pregnant dams was raised to 39.5°C while running at an ambient temperature of 36°C. Bred mice, pregnant or not, continued to increase their running activity, but pregnant mice exercised less from mid‐pregnancy on. Running up to 1 km/hr had no effect on maternal weight gain, number of implantations, number of live fetuses, fetal body weight, and fetal relative brain weight. However, increasing ambient temperature was effective in decreasing maternal weight gain and fetal body weight and increasing fetal relative brain weight. Even though body temperature can be increased significantly by increasing either running rate or ambient temperature, the body temperature increase caused by running appears to have no significant influence on the outcome of pregnancy. At levels in this study, body temperature per se does not appear to be the variable on which to predict fetal effects. This is because only body temperature raised by higher ambient temperature, and not body temperature raised by increased running, was shown to effect a feta

ISSN:0270-3211    

DOI:10.1002/tcm.1770100103

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1990

数据来源: WILEY

摘要:

AbstractIn preparation for a human study of worker exposure to grain fumigants and pesticides, we decided to screen commonly used fumigants for genotoxic effects in vitro. This research strategy was employed to test the possibility that structurally simple chemicals might have similar genotoxic properties in vivo and in vitro. As a first step, we designed our in vitro protocol to mimic to the extent possible, a single in vivo exposure of lymphocytes to fumigants. Golymphocytes were treated with different doses of carbon tetrachloride, carbon disulfide, methyl bromide, chloropicrin, and melathion with and without addition of rat liver homogenate for 1/2 hour, washed free of toxicant, and stimulated with PHA. After culture, the prepared slides were studied for chromosome aberrations and SCEs. Malathion, methyl bromide, and chloropicrin significantly induced SCEs without S‐9. Carbon disulfide alone required S‐9 for significant SCE induction. Chromosome aberrations were significantly increased by malathion and methyl bromide. Carbon tetrachloride failed to induce SCEs or chromosome aberrations with or without S‐9. We concluded from these preliminary studies and other comparable work that the fumigants studied here may be less likely to express genotoxicity in terms of SCEs or chromosome aberrations than ethylene oxide or phosphine given a single short‐term in vivo exposure. The final design of our human study was altered to focus on seasonal worker exposure rather than on a single exposur

ISSN:0270-3211    

DOI:10.1002/tcm.1770100104

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1990

数据来源: WILEY

摘要:

AbstractPhenytoin (5,5‐diphenylhydantoin), a common anticonvulsant drug, is known to produce anomalies in the craniofacial region of animals and humans. Furthermore, recent evidence suggests that phenytoin disrupts craniofacial and neural tube morphogenesis by inhibiting the arachidonic acid cascade, a pathogenesis already implicated for glucocorticoids and hyperglycemia in the palate. This study tested the hypothesis that phenytoin interferes with the arachidonic acid cascade via the same biochemical pathway demonstrated for glucocorticoids. The proposed pathway was tested at two levels. First, indomethacin, an inhibitor of the enzyme cyclooxygenase, was used in culture to block the correction of phenytoin‐induced defects by arachidonic acid. Second, cortexolone, an anti‐glucocorticoid that binds at the glucocorticoid receptor binding site, was tested for its ability to prevent phenytoin‐induced teratogenicity. Eighty‐four percent of the embryos cultured in phenytoin and 93% of those cultured in phenytoin plus arachidonic acid and indomethacin had neural tube and/or craniofacial deformities. In contrast, only 14% of the embryos cultured in phenytoin plus cortexolone were affected. Indomethacin itself produced anomalies in 83% of the exposed embryos. These data are consistent with the hypothesis that the teratogenic action of phenytoin in murine embryo cultures occurs via the glucocorticoid anti‐inflammatory pathway. Thus, the glucocorticoid receptor appears to be responsible for mediating phenytoin‐induced t

ISSN:0270-3211    

DOI:10.1002/tcm.1770100105

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1990

数据来源: WILEY

摘要:

AbstractCaffeine was found to inhibit both type I and type II topoisomerases in vivo as judged by its effects on replicating simian virus 40 (SV40) chromosomes. The study was facilitated by the use of a rapid filter assay for the detection and characterization of topoisomerase inhibitors. The assay, which requires neither purified enzymes nor substrates, was able to identify both antagonists and poisons of type I and type II topoisomerases.

ISSN:0270-3211    

DOI:10.1002/tcm.1770100106

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1990

数据来源: WILEY

摘要:

AbstractThe distribution of heterogeneous cell types within human tumors was examined, and the biological behavior of tumors and different tumor cell lines was evaluated following implantation into surrogate hosts. In situ hybridization and immunohistochemistry were used to examine the expression of oncogenes and localization of the squamous cell carcinoma cell surface‐associated antigens. Increased levels of H‐rasmRNA and p21 protein were present in six tumors, but enhanced c‐mycmRNA expression was observed in just two tumors. The distribution of oncogene mRNA and SCC antigen‐positive cells was not uniform throughout the tumor.Isolation of cells from the tumors was accomplished by cell culture, growth in soft agar, and growth in the nude mouse. One nontumorigenic immortalized cell line, SCC‐83‐01‐82, isolated by passage through soft agar, was treated with 50 μg/ml of methyl methane sulfonate (MMS). These MMS‐converted cells subsequently expressed a tumorigenic phenotype. In situ hybridization of the tumors that developed in nude mice revealed increased c‐mycand H‐rasmRNA expression. Serial passage of the MMS‐converted tumors in vivo was accompanied by consistent enhanced c‐mycexpression. However, the levels of H‐rasand keratin mRNA expression decreased with passage in vitro. Northern blot analysis of c‐mycand H‐rasmRNA levels from the original SCC cell line showed no change in expression following MMS treatment. The data suggest that SCC‐83‐01‐82 is a premalignant cell line established from a mixed cell population in the tumor mass. It can be converted to a malignant phenotype by treatment with MMS, and the persistence of malignancy is under molecular control other than changes in the

ISSN:0270-3211    

DOI:10.1002/tcm.1770100107

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1990

数据来源: WILEY

ISSN:0270-3211    

DOI:10.1002/tcm.1770100108

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1990

数据来源: WILEY

ISSN:0270-3211    

DOI:10.1002/tcm.1770100101

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1990

数据来源: WILEY